Objective To investigate the effect of carbachol on local gut inflammation during entetal resuscitation of rats with bum shock. Method Thirty-eight Wistar rats were subjected to 35%TBSA full thickness scald injury, and enteral fluid was infused into animal intestines via duodenal stomas 30 minutes post bum. The animals were randomly divided into four groups: no resuscitation (Control, n = 8), enteral resuscitation using either a glucose electrolyte solution (GES, n = 10) or GES plus carbachol (60 μg·kg-1,GES/CAR, n = 10), or carbachol alone (CAR, n = 10) .The volumeof GES infusion was based on the Parkland formula (4 ml· 1% TB-SA-1·Kg-1) - All animals were sacrificed 4 hours post bum, and specimens of jejunal tissue were collected to determine the levels of tumor necrosis factor (TNF)-α, nitric oxide (NO), nitric oxide synthase (NOS) and myeloperoxidase (MPO). Serum assays for plasma diamine oxidase (DAO) activities were also performed. Results There were no statistical differences in the intestinal levels of NOS, NO, TNF-α and MPO, and plasma OAO activities, between the GES group and the control group. Compared to the GES group, the GES/CAR group showed significantly lowered levels of intestinal NOS (1.276 ±0.391 vs. 1.818 ±0.436, P＜0.05), NO (0.925 ±0.402 vs. 1.561 ±0.190, P ＜ 0.05, TNF-α (0.87±0.13 vs. 1.94±0.47, P ＜0.01) and MPO (0.465 ±0.092 vs. 0.832±0.214, P＜0.05),and reduction in plasma DAO activites (0.732±0.192 vs. 1.381 ±0.564, P ＜0.05). The CAR group also showed significantly lowered levels of intestinal NOS, NO, TNF-α and MPO and reduced plasma DAO activites, compared to the GES group. Conclusions Theses results suggest that carbachol significantly inhibits the release of proinflammatory mediator and attenuates local inflammation in gut during enteral fluid resuscitation of rats in rats with bum shock. We postulate that carbachol may exert its and-inflammatory effects via the cholinergic anti-inflammatory pathway.

Objective To establish an animal model for study on early oral fluid resuscitation of burn shock so as to provide experimental basis for oral fluid resuscitation of burn shock in wars, accidents or disasters. Methods Male Beagle dogs weighing 11-13 kg were used in the study and the carotis, jugular and duodenum were cannulated respectively for measurement of homodynamics, tissue perfusion and gastrointestinal function. Dogs were subjected to a 35% TBSA full thickness flame injury with 10-mi-nute anesthesia by intravenous injection of propofol 24 hours later, and then randomly and equally divided into two groups(8 dogs in each group) : no fluid resuscitation group (NR group) undergoing no treatment in the first 24 hours post burn and oral fluid resuscitation group ( OR group) undergoing gastric infusion of glucose electrolyte solution (GES) according to Parkland formula. From the second 24 hours post burn, animals in two groups were given delayed Ⅳ fluid resuscitation, and then intravenous nutritional support was initiated at the 72nd hour. The mean arterial pressures (MAP), cardiac output (CO), dp/dt max of left ventricular contractility (dp/dtmax) and plasma volume (PV) were monitored continuously. The pa-rameters of gastrointestinal tissue peffusion, the rates of gastric emptying and intestinal absorption of GES were determined, the morbidity was also recorded at the end of 5-day experiment. Results After 35% TBSA burn injury, MAP, CO,dp/dt max and PV dropped markedly and gastrointestinal tissue perfusion reduced obviously. CO and PV in OR group were significantly higher than those in NG group at 4, 8 and 24 hours after burn. Homodynamic parameters and gastrointestinal tissue perfusion in OR group were pro-moted to pre-injury level at 48 and 72 hours respectively, while homodynamic parameters in NR group did not return to pre-injury level till 72 hours, and gastrointestinal tissue perfusion kept lower than pre-injury till 120 hours post burn. Rates of gastric emptying and intestinal absorption of GES significantly reduced to the lowest level (42% and 37% of pre-injury) at about 4 hours post bum, but did not return to pre-in-jury level till eight hours post bum. Over five days, two out of eight dogs (25%) died in NG group but none in OR group. Conclusions The animal model can exactly simulate the actual circumstance, where oral resuscitation is superior to Ⅳ resuscitation in some aspects in treating early bum shock in wars, accidents and disasters, and provide practical and reliable method for measurement of homodynamic parameters, tissue perfusion, gastric emptying and intestinal absorptive function.

Objective To establish a HPLC method for the simultaneous determination of artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D in the water extract of Artemisia annua L.Methods The analysis was performed on Agilent ZORBAX SB-C18(250 mm×4.6 mm,5 μm)column with a mobile phase of acetonitrile(A)-water(B)and the flow rate of 0.8 mL·min-1 in a gradient elution manner.The column temperature was 30℃.The injection volume was 10 μL,and the detection wavelength was 210 nm.Results Artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D were correlated well linearly with peak area in their respective ranges 1.608 8-16.088 μg(r=0.999 9),0.014 1-0.141 4 μg(r=1),0.185 1-1.850 9 μg(r=0.999 9),0.144 1-1.441 4 μg(r=0.999 9),the average recovery rate(n=6)were 102.44%,97.82%,95.07%,95.55%,and the RSD values were 1.12%,1.44%,1.29%,1.53%.Conclusion This method is convenient and accurate.It has good stability and repeatability,and can be used to simultaneously determine the content of artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D in the water extract of Artemisia annua L.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.